Calcified Tissue International

, Volume 65, Issue 2, pp 173–180

Regulation of Osteogenic Differentiation of Human Bone Marrow Stromal Cells: Interaction Between Transforming Growth Factor-β and 1,25(OH)2 Vitamin D3In Vitro

  • P.  Liu
  • B. O.  Oyajobi
  • R. G. G.  Russell
  • A.  Scutt

DOI: 10.1007/s002239900678

Cite this article as:
Liu, P., Oyajobi, B., Russell, R. et al. Calcif Tissue Int (1999) 65: 173. doi:10.1007/s002239900678

Abstract.

Bone marrow stromal cells are believed to play a major role in bone formation as a major source of osteoprogenitor cells, however, very little is known about how the osteogenic differentiation of these cells is regulated by systemic hormones and local growth factors. We examined the effects of TGF-β and its interaction with 1,25(OH)2 Vitamin D3 [1,25(OH)2D3] on the differentiation and proliferation of human bone marrow stromal cells (hBMSC) in secondary cultures. Alkaline phosphatase (ALP) activity was inhibited by TGF-β (0.1–10 ng/ml) and increased by 1,25(OH)2D3 (50 nM), however, co-treatment of TGF-β and 1,25(OH)2D3 synergistically enhanced ALP activity with maximal stimulation occurring at about 8 days after treatment. This synergistic effect was independent of proliferation because, in contrast to TGF-β alone, combined treatment with TGF-β and 1,25(OH)2D3 had no effect on hBMSC proliferation. As no synergistic effect was seen with combinations of 1,25(OH)2D3 and other osteotrophic growth factors, including BMP-2, IGF-I, and basic fibroblast growth factor (bFGF), it would seem likely that the synergistic interaction is specific for TGF-β. The increased ALP activity was due to an enhancement of 1,25(OH)2D3-induced ALP activity by TGF-β, rather than vice versa. In contrast, TGF-β inhibited 1,25(OH)2D3-induced osteocalcin production. Taken together, these results indicate that TGF-β and 1,25(OH)2D3 act synergistically to stimulate the recruitment of BMSC to the osteoblast lineage. This interaction may play an important role in bone remodeling.

Key words: Human bone marrow stromal cells — TGF-β— 1,25(OH)2D3— Osteogenic differentiation — Osteogenesis.

Copyright information

© 1999 Springer-Verlag New York Inc.

Authors and Affiliations

  • P.  Liu
    • 1
  • B. O.  Oyajobi
    • 1
  • R. G. G.  Russell
    • 1
  • A.  Scutt
    • 1
  1. 1.Human Metabolism and Clinical Biochemistry, Division of Biochemical and Musculoskeletal Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, Great BritainGB